Atherosclerosis, coronary heart disease and peripheral vascular disease are chronic diseases affecting patient mortality around the world. Today, it is estimated that about a million Americans will suffer from a new heart attack every year, and about 500,000 people will have a recurrent attack. Nearly two to three times that many people are affected by this disease around the world. Patients are treated by oral medication, open surgery (such as, coronary artery bypass grafting or CABG) and minimally-invasive endovascular methods (such as, percutaneous transluminal coronary angioplasty or PTCA, percutaneous transluminal angioplasty or PTA).
Percutaneous endovascular intervention is the most frequently performed therapeutic procedure to treat vascular disease using balloon angioplasty and stents. Stents are tubular-shaped devices which hold open a blood vessel or other body lumen (such as a coronary, carotid, iliac, or femoral artery) after delivery and deployment to the target site using a catheter. However, injury to the blood vessel wall from stents may cause neo-intimal hyperplasia, restenosis, and repeat vascularization in a significant number of patients. Drug-eluting stents (DES), with controlled release of antiproliferative or anti-inflammatory agents over time, have reduced the restenosis rates and repeat revascularization rates compared to bare metal stents (BMS). Today, drug-eluting stents are implanted in over 2 million patients per year, worldwide, to treat various forms of cardiovascular and vascular disease.
Though DES have significantly improved the treatment efficacy and reduced repeat revascularizations compared to BMS, their long-term safety is in question. DES have been associated with an increased risk of very late thrombosis beyond one year, and in some cases up to three to five years, after stent implantation. Stent thrombosis is a rare but serious complication that occurs with DES and BMS immediately after stent placement inside the artery. Sub-optimal stent deployment, incomplete stent apposition against the artery wall, inadequate platelet inhibition, chronic inflammation and delayed arterial healing are some factors that cause acute or sub-acute thrombosis within the first six months after stent implantation. In particular, chronic inflammation and delayed healing are more prevalent with DES than BMS, causing higher incidence of late thrombotic events beyond six months.
Similarly, bioresorbable polymeric stents and bioresorbable vascular scaffolds (BVS) currently undergoing clinical evaluation also show higher inflammation, higher risk for thrombosis, and lower biocompatibility compared to BMS and metallic DES. As a result, polymeric stents are also prone to late stent thrombosis beyond six months after stent implantation.
Intense review of clinical trial data by regulatory agencies and professional societies led to the recommendation of extending the dual anti-platelet drug therapy for at least 12 months and in some cases two years after drug-eluting stent implantation to mitigate the risk of thrombosis. The use of prolonged oral antiplatelet therapy may be costly and increased the economic burden on healthcare. More recent reports indicate that, for patients that received a coronary stent, the need for subsequent cardiac and non-cardiac surgery is associated with considerable risk of ischemic and bleeding events due to the prolonged use of dual anti-platelet therapy (DAPT) in the perioperative phase. Stopping DAPT for surgery in stented patients lowers the risk of bleeding but increases the risk of thrombosis and ischemic events. Such prolonged use may also lead to other side effects, especially in patients with other comorbidities. In addition, patients are often non-compliant to daily oral medication which increases their risk for the incidence of clinical adverse events.
What is needed are compositions and materials for making coatings and medical devices with biohealing and biocompatibility properties to reduce the risk of thrombotic events (acute, sub-acute and late), reduce the dependence of patients on DAPT after implanting a medical device, and reduce other adverse clinical events associated with DES and implantable medical devices.